Double-negative (CD27−IgD−) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations
AuthorCentuori, Sara M.
Gomes, Cecil J.
Kim, Samuel S.
Putnam, Charles W.
Larsen, Brandon T.
Garland, Linda L.
Mount, David W.
Martinez, Jesse D.
AffiliationUniv Arizona, Canc Ctr
Univ Arizona, Canc Biol Grad Interdisciplinary Program
Univ Arizona, Dept Surg
Univ Arizona, Dept Med, Div Hematol Oncol
Univ Arizona, Dept Mol & Cellular Biol
Univ Arizona, Cell & Mol Med
MetadataShow full item record
PublisherBIOMED CENTRAL LTD
CitationDouble-negative (CD27−IgD−) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations 2018, 16 (1) Journal of Translational Medicine
Rights© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractBackground: The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A(+)CD27(-)IgD(-). These CD27(-)IgD(-)(double-negative) B cells have previously been characterized as unconventional memory B cells and have been detected in some autoimmune diseases and in the elderly population but have not been detected previously in tumor tissue. Methods: A total of 15 fresh untreated NSCLC tumors and 15 matched adjacent lung control tissues were dissociated and analyzed by intracellular flow cytometry to detect the B cell-related markers CD79A, CD27 and IgD. All CD79A(+) B cells subsets were classified as either naive (CD27(-)IgD(+)), affinity-matured (CD27(+)IgD(-)), early memory/germinal center cells (CD27(+)IgD(+)) or double-negative B cells (CD27(-)IgD(-)). Association of double-negative B cells with clinical data including gender, age, smoking status, tumor diagnosis and pathologic differentiation status were also examined using the logistic regression analysis for age and student's t-test for all other variables. Associations with other B cell subpopulations were examined using Spearman's rank correlation. Results: We observed that double-negative B cells were frequently abundant in lung tumors compared to normal adjacent controls (13 out of 15 cases), and in some cases made up a substantial proportion of the total B cell compartment. The presence of double-negative cells was also found to be inversely related to the presence of affinity-matured B cells within the tumor, Spearman's coefficient of -0.76. Conclusions: This study is the first to observe the presence of CD27(-)IgD(-)double-negative B cells in human NSCLC and that this population is inversely correlated with traditional affinity-matured B cell populations.
NoteOpen access journal.
VersionFinal published version
SponsorsNational Cancer Institute [R01 CA129688, R01 CA129688-03S1, T32 CA09213, P30CA023074]; Geographic Management of Cancer Health Disparities Program (GMaP) Region 3, an initiative of the National Cancer Institute's Center to Reduce Cancer Health Disparities
- Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells.
- Authors: Klein U, Rajewsky K, Küppers R
- Issue date: 1998 Nov 2
- Antigen-Presenting Intratumoral B Cells Affect CD4<sup>+</sup> TIL Phenotypes in Non-Small Cell Lung Cancer Patients.
- Authors: Bruno TC, Ebner PJ, Moore BL, Squalls OG, Waugh KA, Eruslanov EB, Singhal S, Mitchell JD, Franklin WA, Merrick DT, McCarter MD, Palmer BE, Kern JA, Slansky JE
- Issue date: 2017 Oct
- B-cell subsets in the joint compartments of seropositive and seronegative rheumatoid arthritis (RA) and No-RA arthritides express memory markers and ZAP70 and characterize the aggregate pattern irrespectively of the autoantibody status.
- Authors: Michelutti A, Gremese E, Morassi F, Petricca L, Arena V, Tolusso B, Alivernini S, Peluso G, Bosello SL, Ferraccioli G
- Issue date: 2011 Sep-Oct
- Bone marrow B lymphocytes in multiple myeloma and MGUS: Focus on distribution of naïve cells and memory subsets.
- Authors: Pojero F, Casuccio A, Giambanco C, Bulati M, Buffa S, Di Bassiano F, Gervasi F, Caruso C, Colonna Romano G
- Issue date: 2016 Oct
- Impaired CD27<sup>+</sup>IgD<sup>+</sup> B Cells With Altered Gene Signature in Rheumatoid Arthritis.
- Authors: Hu F, Zhang W, Shi L, Liu X, Jia Y, Xu L, Zhu H, Li Y, Xu D, Lu L, Qiu X, Liu W, Qiao J, Wang Y, Li Z
- Issue date: 2018